Neonatal mice lacking neuronal nitric oxide synthase are less vulnerable to hypoxic-ischemic injury.

We hypothesized that elimination of neuronal nitric oxide synthase (nNOS) by targeted disruption of the nNOS gene would result in amelioration of damage seen after hypoxia-ischemia in the developing brain since nitric oxide (NO) has been implicated in glutamate-mediated neurotoxicity after ischemia. Both wildtype and nNOS-deficient pups were subjected to focal ischemia followed by 1.5 h of hypoxia at Postnatal Day 7. Seven days later, brains of surviving animals were analyzed for damage. The nNOS-deficient pups (n = 17) had less histopathologic evidence of injury in both the hippocampus (P = 0.008) and the cortex (P = 0.0008) than the wildtype (n = 30) mice. When injured, the nNOS-deficient mice had damage that was limited to the hippocampus. These results support a role for neuronally produced NO in injury after perinatal hypoxia-ischemia.